Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsSmith, K A
Filbey, K J
Reynolds, L A
Hewitson, J P
Maizels, R M
MetadataShow full item record
AbstractHelminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency.
CitationLow-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths. 2016, 9 (2):428-43 Mucosal Immunol
AffiliationTwincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hanover and the Helmholtz Centre for Infection Research, Hanover, Germany.
The following license files are associated with this item:
- IL-6 controls susceptibility to helminth infection by impeding Th2 responsiveness and altering the Treg phenotype in vivo.
- Authors: Smith KA, Maizels RM
- Issue date: 2014 Jan
- IRF-8 regulates expansion of myeloid-derived suppressor cells and Foxp3+ regulatory T cells and modulates Th2 immune responses to gastrointestinal nematode infection.
- Authors: Valanparambil RM, Tam M, Gros PP, Auger JP, Segura M, Gros P, Jardim A, Geary TG, Ozato K, Stevenson MM
- Issue date: 2017 Oct
- Expansion and activation of CD4(+)CD25(+) regulatory T cells in Heligmosomoides polygyrus infection.
- Authors: Finney CA, Taylor MD, Wilson MS, Maizels RM
- Issue date: 2007 Jul
- Regulatory T-cell neutralization in mice during filariasis helps in parasite clearance by enhancing T helper type 17-mediated pro-inflammatory response.
- Authors: Pathak M, Sharma P, Sharma A, Verma M, Srivastava M, Misra-Bhattacharya S
- Issue date: 2016 Feb
- Concurrent infection with Heligmosomoides polygyrus suppresses anti-Plasmodium yoelii protection partially by induction of CD4(+)CD25(+)Foxp3(+) Treg in mice.
- Authors: Tetsutani K, Ishiwata K, Ishida H, Tu L, Torii M, Hamano S, Himeno K, Hisaeda H
- Issue date: 2009 Oct